Environmental or occupational exposure to a broad variety of chemical agents can alter normal endocrine function. The effects of these "endocrine disruptors" (ED) can have serious health implications including deleterious effects to reproductive capacity, fetal development, the immune system, and carcinogenesis. Current animal tests are expensive, use a large number of animals, and are not necessarily applicable to humans. Thus, a validated, human in vitro method to identify ED is an area of great importance. This research project will validate an organotypic EpiVaginal tissue model for Tier 1 screening of chemicals with endocrine disrupting potential. Phase I research will validate MatTek's organotypic vaginal-ectocervical (EpiVaginalTM) tissue model for use in identifying ED. A battery of 75 model compounds with known ED activity will be selected from the revised ICCVAM list of recommended substances. The production of estrone by the tissue model and changes to tissue morphology and gene expression will be monitored as biomarkers of ED. A prediction model for ED with be finalized and the test method will undergo formal validation in a multi-center, GLP study. In addition, reproducibility of the assay method and adaptation of the method to a high throughput screen format will be investigated. If successful, the proposed method will have high impact in environmental chemical safety programs and ultimately will reduce the effect of these chemicals on human health. PUBLIC HEALTH RELEVANCE: Validation an in vitro organotypic tissue based assay to screen for endocrine disrupting potential is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The assay method will be adapted to a high throughput format to allow rapid and low- cost screening of chemicals. The organotypic tissue based in vitro screening method will have enormous environmental and public health significance.